Negative regulation of BMP/Smad signaling by Tob in osteoblasts
Negative regulation of BMP/Smad signaling by Tob in osteoblasts
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DOI：
10.1016/s0092-8674(00)00211-7
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发表时间：
2000-12-22
期刊：
影响因子：
64.5
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Yoshida, Y;Tanaka, S;Yamamoto, T
骨形态发生蛋白（BMP）通过Smad蛋白调控成骨细胞的增殖和分化。在这里，我们表明，Tob，一个新兴的抗增殖蛋白家族的成员，是成骨细胞中BMP/Smad信号的负调节因子。携带靶向缺失tob基因的小鼠由于成骨细胞数量的增加而具有更大的骨量。在tob缺陷小鼠中，响应于BMP 2的原位骨形成增加。Tob的过度产生抑制BMP 2诱导的Smad介导的转录激活。最后，Tob与受体调节的Smads（Smad 1，5和8）相关联，并在BMP 2刺激后与核小体中的Smads共定位。结果表明，Tob通过抑制受体调节的Smad蛋白的活性来负调节成骨细胞的增殖和分化。
Bone morphogenetic protein (BMP) controls osteoblast proliferation and differentiation through Smad proteins. Here we show that Tob, a member of the emerging family of antiproliferative proteins, is a negative regulator of BMP/Smad signaling in osteoblasts. Mice carrying a targeted deletion of the tob gene have a greater bone mass resulting from increased numbers of osteoblasts. Orthotopic bone formation in response to BMP2 is elevated in tob-deficient mice. Overproduction of Tob represses BMP2-induced, Smad-mediated transcriptional activation. Finally, Tob associates with receptor-regulated Smads (Smad1, 5, and 8) and colocalizes with these Smads in the nuclear bodies upon BMP2 stimulation. The results indicate that Tob negatively regulates osteoblast proliferation and differentiation by suppressing the activity of the receptor-regulated Smad proteins.